Meta-analysis of polycystic kidney disease expression profiles defines strong involvement of injury repair processes.
Am J Physiol Renal Physiol
; 312(4): F806-F817, 2017 04 01.
Article
em En
| MEDLINE
| ID: mdl-28148532
ABSTRACT
Polycystic kidney disease (PKD) is a major cause of end-stage renal disease. The disease mechanisms are not well understood and the pathogenesis toward renal failure remains elusive. In this study, we present the first RNASeq analysis of a Pkd1-mutant mouse model in a combined meta-analysis with other published PKD expression profiles. We introduce the PKD Signature, a set of 1,515 genes that are commonly dysregulated in PKD studies. We show that the signature genes include many known and novel PKD-related genes and functions. Moreover, genes with a role in injury repair, as evidenced by expression data and/or automated literature analysis, were significantly enriched in the PKD Signature, with 35% of the PKD Signature genes being directly implicated in injury repair. NF-κB signaling, epithelial-mesenchymal transition, inflammatory response, hypoxia, and metabolism were among the most prominent injury or repair-related biological processes with a role in the PKD etiology. Novel PKD genes with a role in PKD and in injury were confirmed in another Pkd1-mutant mouse model as well as in animals treated with a nephrotoxic agent. We propose that compounds that can modulate the injury-repair response could be valuable drug candidates for PKD treatment.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regeneração
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Traumatismo por Reperfusão
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Rim Policístico Autossômico Dominante
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Injúria Renal Aguda
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Transcriptoma
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Rim
Tipo de estudo:
Prognostic_studies
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Systematic_reviews
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article